Cytoprotective and Neurotrophic Effects of Octadecaneuropeptide (ODN) in in vitro and in vivo Models of Neurodegenerative Diseases

Abstract

Octadecaneuropeptide (ODN) and its precursor diazepam-binding inhibitor (DBI) are peptides belonging to the family of endozepines. Endozepines are exclusively produced by astroglial cells in the central nervous system of mammals, and their release is regulated by stress signals and neuroactive compounds. There is now compelling evidence that the gliopeptide ODN protects cultured neurons and astrocytes from apoptotic cell death induced by various neurotoxic agents. In vivo , ODN causes a very strong neuroprotective action against neuronal degeneration in a mouse model of Parkinson's disease. The neuroprotective activity of ODN is based on its capacity to reduce inflammation, apoptosis, and oxidative stress. The protective effects of ODN are mediated through its metabotropic receptor. This receptor activates a transduction cascade of second messengers to stimulate protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathways, which in turn inhibits the expression of proapoptotic factor Bax and the mitochondrial apoptotic pathway. In N2a cells, ODN also promotes survival and stimulates neurite outgrowth. During the ODN-induced neuronal differentiation process, numerous mitochondria and peroxisomes are identified in the neurites and an increase in the amount of cholesterol and fatty acids is observed. The antiapoptotic and neurotrophic properties of ODN, including its antioxidant, antiapoptotic, and pro-differentiating effects, suggest that this gliopeptide and some of its selective and stable derivatives may have therapeutic value for the treatment of some neurodegenerative diseases.

GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress

“…Acetylation of Rictor promotes cancer cell survival via the attenuation of apoptosis (Masui et al, 2015). Cytoprotective signaling is essential to for the survival of any cell under stress, and it is crucial for non-regenerative tissues like cardiomyocytes, neurons, and skeletal muscle cells (He et al, 2022, Masmoudi-Kouki et al, 2020). Pathological conditions (e.g.…”

The diazepam binding inhibitor’s modulation of the GABA-A receptor is subunit-dependent

“…To evaluate and compare the effects of the positive BZD modulator, FZM, the negative BZD modulator, DMCM and DBI, we applied GABA EC20 concentration and then co-applied FZM (10μM), DMCM (10μM) or DBI (50μM) with GABA EC20 (Fig 3A). FZM and DMCM concentrations are saturating [34, 35], and the concentration of DBI was selected to reflect the level of DBI and cleavage products measured in rat brains [36]. FZM (10μM) significantly increased GABA currents from oocytes expressing α 3 β 3 γ 2L and α 5 β 3 γ 2L GABARs 2.7- and 2.0 fold, respectively (Fig.…”

A bibliometric analysis of the recent advances in diazepam from 2012 to 2021

“…Intraventricular administration will induce conflict and anxiety behavior, so it is called a diazepam binding inhibitor(DBI) ( Guidotti et al, 1983 ; Tonon et al, 2020 ). In the study of DBI, researchers found that it is a peptide of the network peptide family, which is produced by astrocytes, regulates energy metabolism, and inhibits apoptosis caused by oxidative stress and acts as a neuronal protector ( Ghouili et al, 2018 ; Masmoudi-Kouki et al, 2020 ). However, there are very few studies on astrocytes and oxidative stress related to diazepam.…”